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PubMed2003

Thermoregulatory behavior of the crayfish Procambarus clarki in a burrow environment.

The behavioral thermoregulation of the red swamp crayfish, Procambarus clarki, was investigated in its burrow environment. In the field, air and water temperatures within crayfish burrows fluctuated less compared with surface temperatures in the Mojave Desert. However, crayfish could still experience sub-optimal temperature regimes inside burrows. In the laboratory, P. clarki heated and cooled more rapidly in water than in air. In a thermal gradient, the crayfish selected a water temperature of 22 degrees C and avoided water temperatures above 31 degrees C and below 12 degrees C. Observations of behavior in an artificial burrow showed that P. clarki displayed three main shuttling behaviors between water and air in response to temperature. The number of bilateral emersions and emigrations, as well as the amount of time spent in air (in a 24 h period), were significantly greater at 34 degrees C than at 12, 16, 22 or 28 degrees C. This reflected an increased use of the behavioral thermoregulation at temperatures approaching the critical thermal maximum of this species. Upon migrating from 34 degrees C water into 38 degrees C air, crayfish body temperature decreased significantly. These periods of emersion were interspersed with frequent dipping in the water, allowing the crayfish to gain the benefits of evaporative cooling, without the physiological costs incurred by long-term exposure to air.

Air↗

PubMed2000

A folding variant of alpha-lactalbumin with bactericidal activity against Streptococcus pneumoniae.

This study describes an alpha-lactalbumin folding variant from human milk with bactericidal activity against antibiotic-resistant and -susceptible strains of Streptococcus pneumoniae. The active complex precipitated with the casein fraction at pH 4.6 and was purified from casein by a combination of anion exchange and gel chromatography. Unlike other casein components, the active complex was retained on the ion-exchange matrix and eluted only with high salt. The eluted fraction showed N-terminal and mass spectrometric identity with human milk alpha-lactalbumin, but native alpha-lactalbumin had no bactericidal effect. Spectroscopic analysis demonstrated that the active form of the molecule was in a different folding state, with secondary structure identical to alpha-lactalbumin from human milk whey, but fluctuating tertiary structure. Native alpha-lactalbumin could be converted to the active bactericidal form by ion-exchange chromatography in the presence of a cofactor from human milk casein, characterized as a C18:1 fatty acid. Analysis of the antibacterial spectrum showed selectivity for streptococci; Gram-negative and other Gram-positive bacteria were resistant. The folding variant of alpha-lactalbumin is a new example of naturally occurring molecules with antimicrobial activity.

Anti-Bacterial Agents↗

PubMed2004

Combined electronic structure/molecular dynamics approach for ultrafast infrared spectroscopy of dilute HOD in liquid H2O and D2O.

We present a new approach that combines electronic structure methods and molecular dynamics simulations to investigate the infrared spectroscopy of condensed phase systems. This approach is applied to the OH stretch band of dilute HOD in liquid D2O and the OD stretch band of dilute HOD in liquid H2O for two commonly employed models of water, TIP4P and SPC/E. Ab initio OH and OD anharmonic transition frequencies are calculated for 100 HOD x (D2O)n and HOD x(H2O)n (n = 4-9) clusters randomly selected from liquid water simulations. A linear empirical relationship between the ab initio frequencies and the component of the electric field from the solvent along the bond of interest is developed. This relationship is used in a molecular dynamics simulation to compute frequency fluctuation time-correlation functions and infrared absorption line shapes. The normalized frequency fluctuation time-correlation functions are in good agreement with the results of previous theoretical approaches. Their long-time decay times are 0.5 ps for the TIP4P model and 0.9 ps for the SPC/E model, both of which appear to be somewhat too fast compared to recent experiments. The calculated line shapes are in good agreement with experiment, and improve upon the results of previous theoretical approaches. The methods presented are simple, and transferable to more complicated systems.

Journal Article↗

PubMed1999

Yersinia enterocolitica type III secretion-translocation system: channel formation by secreted Yops.

'Type III secretion' allows extracellular adherent bacteria to inject bacterial effector proteins into the cytosol of their animal or plant host cells. In the archetypal Yersinia system the secreted proteins are called Yops. Some of them are intracellular effectors, while YopB and YopD have been shown by genetic analyses to be dedicated to the translocation of these effectors. Here, the secretion of Yops by Y.enterocolitica was induced in the presence of liposomes, and some Yops, including YopB and YopD, were found to be inserted into liposomes. The proteoliposomes were fused to a planar lipid membrane to characterize the putative pore-forming properties of the lipid-bound Yops. Electrophysiological experiments revealed the presence of channels with a 105 pS conductance and no ionic selectivity. Channels with those properties were generated by mutants devoid of the effectors and by lcrG mutants, as well as by wild-type bacteria. In contrast, mutants devoid of YopB did not generate channels and mutants devoid of YopD led to current fluctuations that were different from those observed with wild-type bacteria. The observed channel could be responsible for the translocation of Yop effectors.

Amino Acid Sequence↗

PubMed2006

Ordered motor-unit firing behavior in acute cerebellar stroke.

It is known that at any given force level, the lower-threshold motor units generally fire at greater rates than the higher-threshold units during isometric tasks of extremity muscles. In addition to this hierarchical arrangement, firing rates of motor units fluctuate in unison with nearly no time delay; an observation that has led to the concept of common drive, a basic motoneuronal rule. Although it is established that the cerebellum plays a critical function in motor control, its role in the genesis, triggering, selection, and monitoring of motor-unit firing pattern discharges during isometric tasks is unknown. We applied an electromyographic (EMG) decomposition technique, known as precision decomposition, to accurately identify motor-unit firing times from the EMG signal recorded from the first dorsal interosseous muscle to unravel the features of motor-unit firings in three patients presenting a unilateral cerebellar stroke and exhibiting an acute cerebellar syndrome. We observed ataxic isometric force during visually guided abduction of the index finger on the affected side. However, the hierarchical response of individual motor units was spared. Furthermore, acute cerebellar ataxia was not associated with a loss of the common drive.

Acute Disease↗

PubMed1997

Efficacy of bilateral pallidotomy.

Unilateral pallidotomy is a safe and effective treatment for medically refractory bradykinetic Parkinson's disease, especially in those patients with levodopa-induced dyskinesia and severe on-off fluctuations. The efficacy of bilateral pallidotomy is less certain. The authors completed 11 of 12 attempted bilateral pallidotomies among 150 patients undergoing pallidotomy at New York University. In all but one patient, the pallidotomies were separated by at least 9 months. Patients were selected for bilateral pallidotomy if they exhibited bilateral rigidity, bradykinesia, or levodopa-induced dyskinesia prior to treatment or if they exhibited disease progression contralateral to their previously treated side. The Unified Parkinson's Disease Rating Scale (UPDRS) and timed upper-extremity tasks of the Core Assessment Protocol for Intracerebral Transplantation (CAPIT) were administered to all 12 patients in the "off" state (12 hours without receiving medications) preoperatively and again at 6 and 12 months after each procedure. The median UPDRS and contralateral CAPIT scores improved 60% following the initial procedure (p = 0.008, Wilcoxon rank sums test). The second pallidotomy generated only an additional 10% improvement in the UPDRS and CAPIT scores ipsilateral to the original procedure (p = 0.05). Worsened speech was observed in two cases. In the 12th case, total speech arrest was noted during test stimulation. Speech returned within minutes after stimulation was halted. Lesioning was not performed. These results indicate that bilateral pallidotomy has a narrow therapeutic window. Motor improvement ipsilateral to the first lesion leaves little room for further improvement from the second lesion and the risk of speech deficit is greatly enhanced. Chronic pallidal stimulation contralateral to a previously successful pallidotomy may prove to be a safer alternative for the subset of patients who require bilateral procedures.

Journal Article↗

PubMed1999

International variation in reported livebirth prevalence rates of Down syndrome, adjusted for maternal age.

Reported livebirth prevalence of Down syndrome (DS) may be affected by the maternal age distribution of the population, completeness of ascertainment, accuracy of diagnosis, extent of selective prenatal termination of affected pregnancies, and as yet unidentified genetic and environmental factors. To search for evidence of the latter, we reviewed all published reports in which it was possible to adjust both for effects of maternal age and for selective termination (where relevant). We constructed indices that allowed direct comparisons of prevalence rates after standardising for maternal age. Reference rates were derived from studies previously identified as having near complete ascertainment. An index value significantly different from 1 may result from random fluctuations, as well as from variations in the factors listed above. We found 49 population groups for which an index could be calculated. Methodological descriptions suggested that low values could often be attributed to under-ascertainment. A possible exception concerned African-American groups, though even among these most acceptable studies were compatible with an index value of 1. As we have reported elsewhere, there was also a suggestive increase in rates among US residents of Mexican or Central American origin. Nevertheless, our results suggest that "real" variation between population groups reported to date probably amounts to no more than +/-25%. However, reliable data in many human populations are lacking including, surprisingly, some jurisdictions with relatively advanced health care systems. We suggest that future reports of DS livebirth prevalence should routinely present data that allow calculation of an index standardised for maternal age and adjusted for elective prenatal terminations.

Adolescent↗

PubMed2000

Four-year longitudinal course of TMD symptoms in an adult population and the estimation of risk factors in relation to symptoms.

AIMS: To investigate the natural course of symptoms of temporomandibular disorders (TMD) in a non-patient population and to estimate the strength of the relationship between several hypothesized risk factors and precipitation and perpetuation of the symptoms. METHODS: A total of 672 randomly selected citizens of Okayama City was requested to answer the same self-administered questionnaire that they had answered 4 years earlier. The mailed questionnaire failed to reach 58 subjects at the second survey, and 367 of the remaining subjects (59.8%) responded. The fluctuation of TMD symptoms was assessed by comparison of 6 pairs of answers for questions regarding temporomandibular joint (TMJ) pain, limitation of mouth opening, TMJ noise, headache, neck pain, and shoulder stiffness. Six factors (age under 40, female, clenching habit, history of extrinsic trauma, sleep disturbance, and family history of TMD) were tested for their relative risk in precipitating and perpetuating each TMD symptom by the use of its confidence interval to define significance. RESULTS: The incidence of TMD symptoms ranged from 6.1% (TMJ pain) to 12.9% (TMJ noise). More than half of the subjects who had reported TMJ and neck pain at the initial survey no longer reported these symptoms at the second survey, whereas TMJ noise and shoulder stiffness remained in more than 70% of the subjects. Individuals under 40 years old had a 3.3:1 increased risk of precipitating TMJ noise (P < 0.01), individuals with a history of extrinsic trauma had a 2.85:1 increased risk of precipitating limited mouth opening (P < 0.01), and females had a 2.81:1 increased risk of perpetuating TMJ pain (P < 0.01). CONCLUSION: The possible etiologic significance of these factors in TMD should be validated by future research.

Age Distribution↗

PubMed1995

In vitro cultivation of the human microsporidium Vittaforma corneae: development and effect of albendazole.

When in vitro growth of Vittaforma corneae was tested using MDCK, MRC-5, XEN, L-929 and FHM cell lines, propagation occurred only in MDCK, MRC-5 and XEN cells. The intervals required for the various stages of the life cycle to develop were the same in all the cell lines tested. The MDCK cell line was selected to support the growth of V. corneae in vitro and provide the system for in vitro testing of drugs. The weekly output of V. corneae spores from the MDCK cell monolayer was monitored over a 61-week period during which there were fluctuations but no definite increase or decrease in output. Albendazole at 2.1 or 4.2 micrograms/ml in MEM was tested against V. corneae in MDCK cell monolayers and showed antimicrosporidial activity. The percentage of infected cells was reduced in the presence of the drug and there were ultrastructural abnormalities in all stages of the life cycle. The drug prevents parasite division.

Albendazole↗

PubMed1998

[Biochemical markers of bone metabolism].

Markers of bone metabolism can be utilized for selection of treatment and/or evaluation of the treatment, and possibly decision-making to start treatment. Resorption markers are sensitive to detect changes in bone metabolism but show higher day-to-day variation, and formation markers are less sensitive but show less fluctuation. Among these markers, deoxypyridinoline, NTx, and CTx are utilized for short-term judgement of efficacy during the early phase of anti-resorptive treatment, such as bisphosphonate and hormone replacement therapy. The coefficients of day-by-day variations in these resorption markers are 8-14%. Thus, 20 (approximately 30)% or more change in marker levels may be necessary to detect the efficacy in individual patients on anti-resorptive therapy. The formation markers can be utilized for monitoring the degree of excessive suppression during the late phase of treatment by anti-resorptive treatment, possibly later than 6 months following initial treatment.

Biomarkers↗

PubMed2005

Longitudinal fluctuation of antibodies to extractable nuclear antigens in systemic lupus erythematosus.

OBJECTIVE: To examine the appearance, persistence, and disappearance of anti-extractable nuclear antigen (ENA, Sm, U1-RNP, Ro/SSA, and La/SSB) and anti-native DNA (dsDNA) antibodies during systemic lupus erythematosus (SLE) followup. METHODS: One hundred and thirty patients who fulfilled American College of Rheumatology classification criteria for SLE with at least 5 yearly anti-ENA and dsDNA tests between 1987-2002 were retrospectively selected. Four longitudinal antibody data patterns were considered for each antibody: always absent, always present, absent at diagnosis with positive seroconversion, and present at diagnosis with negative seroconversion. RESULTS: Antibodies to Ro/SSA were present in 47%, U1-RNP in 36%, DNA in 32%, Sm in 23%, and La/SSB in 7% of patients. Among patients ever positive for a given autoantibody, the frequency of the "always present" pattern was 52% for anti-Ro/SSA, 38% for U1-RNP, 17% for Sm, 11% for La/SSB, and 9% for DNA antibodies; the frequency of positive seroconversion was 56% for anti-La/SSB, 33% for DNA, 26% for Sm, 21% for U1-RNP, and 15% for Ro/SSA. Time to positive seroconversion varied from 1 to 8 years after diagnosis. Among patients with a positive test at diagnosis the frequency of those remaining positive between the 2nd and 4th year of followup decreased to 39-78%, depending upon autoantibody specificity; between the 5th and 10th years this rate was 20-75%. Antibody data pattern frequency differed significantly among autoantibody specificities except between anti-U1-RNP and Ro/SSA (p = 0.15) and between anti-DNA and Sm antibodies (p = 0.29). CONCLUSION: The high frequency of longitudinal fluctuation in anti-ENA antibodies suggests that a periodic reappraisal may be appropriate in seronegative patients with a suspect diagnosis of SLE. The clinical significance of such fluctuation deserves future study.

Antibodies, Antinuclear↗

PubMed2002

Patterns of intermediate host use and levels of association between two conflicting manipulative parasites.

For many parasites with complex life cycles, manipulation of intermediate host phenotypes is often regarded as an adaptation to increase the probability of successful transmission. This phenomenon creates opportunities for either synergistic or conflicting interests between different parasite species sharing the same intermediate host. When more than one manipulative parasite infect the same intermediate host, but differ in their definitive host, selection should favour the establishment of a negative association between these manipulators. Both Polymorphus minutus and Pomphorhynchus laevis exploit the amphipod Gammarus pulex as intermediate host but differ markedly in their final host, a fish for P. laevis and a bird for P. minutus. The pattern of host use by these two conflicting manipulative parasites was studied. Their incidence and intensity of infection and their distribution among G. pulex were first examined by analysing three large samples of gammarids collected from the river Tille, Eastern France. Both parasites had low prevalence in the host population. However, temporal fluctuation in the level of parasitic infection was observed. Overall, prevalence of both parasite species was higher in male than in female G. pulex. We then assessed the degree of association between the two parasites among their intermediate hosts, using two different methods: a host-centred measure and a parasite-centred measure. Both measures gave similar results; showing random association between the two acanthocephalan species in their intermediate hosts. We discuss our results in relation to the selective forces and ecological constraints that may determine the pattern of association between conflicting manipulative parasites.

Acanthocephala↗

PubMed2000

Hereditary progressive dystonia with marked diurnal fluctuation.

Hereditary progressive dystonia with marked diurnal fluctuation or the strictly defined dopa-responsive dystonia (HPD/DRD) is an autosomally dominantly inherited dystonia caused by abnormalities of the gene of the GTP cyclohydrolase I (GCH 1) located on the 14q22. 1-q22.2. The heterozygotic gene abnormality induces partial decrement of tetrahydrobiopterin (BH4) and affects synthesis of tyrosine hydroxylase (TH) rather selectively. The reduction of TH exists at the terminals of the nigrostriatal (NS) dopamine (DA) neuron, predominantly in the ventral area of the striatum and disfacilitates the D1 receptor-striatal direct pathway. This consequently disinhibit the inhibitory efferent pathways and develops postural dystonia via the particular descending pathways to the reticulospinal tract and postural tremor via the ascending pathways to the ventralis lateralis (VL) nucleus of the thalamus. This also inhibits the efferents to the superior colliculus, and affects voluntary saccade but spares that to the pedunculo-pontine nucleus (PPN) preserving locomotive movement clinically. The DA-D2 receptors, the striatal indirect pathways or the efferent connecting to these pathways are not involved in the pathophysiology of HPD/DRD. So parkinsonian plastic rigidity, parkinsonian resting tremor, cogwheel rigidity or levodopa induced dyskinesia are not observed. In some patients, particularly in compound hetereozygotes, there are symptoms suggesting the involvement of serotonergic neurons or those thought to be caused by exaggeration of DA-D2 receptors. Neuropathologically there is no degenerative changes. Clinical laboratory examinations suggest that levels of TH and DA activities are around 20% of the normal values throughout the course of illness. Therefore, the age-dependent clinical course, marked progression in the first one and one half decades, its subsiding in the third decade and almost stationary course from the fourth decade are just the reflection of age-related decremental variation of the TH activities at the terminal of the normal NS-DA neuron. The diurnal fluctuation is also the reflection of circadian oscillation of the TH activities at the terminal. Functional maturation of the striatal indirect pathways in the first one and one half decades and developmental decremental variation of the DA-D2 receptor in the first three decades also reflect in the age-dependent variation of symptoms by modulating the background tone of muscle. The later functional development of the ascending efferents of the basal ganglia to the thalamus, may cause the postural tremor which appears in the second decade and becomes predominant in the fourth decade. Early decrease of TH due to deficiency of BH4 in HPD/DRD also affects the DA-D4 receptor of the tuberoinfundibular DA neuron and cause stagnation of increase of body length in childhood. With normal preservation of the fundamental function of the NS-DA neuron, levodopa, by replacing the DA content at the terminal, alleviates the motor symptoms completely and the effects sustain without any side effects. Levodopa also improves the short body length, if it is administrated before puberty. Up to now 60 mutations have been detected in the GCH 1 gene. The locus of mutation differs among families except for two pare of families with different ethnic background which showed identical mutations. Experimentally, one abnormal heterozygotic gene decreased the production of the enzyme to less than 50%, e.g. some below 20% and others around 30-40%, which clinically as symptomatic patients and asymptomatic carriers, respectively. Other experiments show dominant negative effects which differ among families or the loci of mutation. These might be the background for developing the intra-familial variation, that is, in some there is anticipation, and in the other the symptoms and clinical course are identical or vary in a family without any relation to the generation. (ABSTRACT TRUNCATED)

Animals↗

PubMedDate not supplied

Hormesis: an adaptive expectation with emphasis on ionizing radiation.

Non-linear fitness gradients with maxima between extremes are expected for any environmental variable to which free-living populations are exposed. For exceedingly toxic agents, including ionizing radiation, such deviations from linearity are close to zero exposure and are conventionally called hormesis. Accordingly, hormesis is an extreme version of the non-linear fitness gradients for general environmental stresses such as temperature fluctuations, for which maximum fitness occurs at the moderate temperature fluctuations to which free-living populations are most commonly exposed. Some metabolic reserves should occur under moderate temperature stresses because of the need for pre-adaptation enabling survival during exposure to occasional periods of more extreme stress, especially at species borders where selection for stress resistance is likely to be most intense. Because heat shock proteins are induced by all stresses, adaptation to extreme temperatures should translate into adaptation to other stresses. Consequently, metabolic reserves from adaptation to extreme temperatures in the past should translate into protection from correlated abiotic stresses, especially in human populations where modern cultural processes are now ameliorating exposure to extreme stresses. Ambient and man-made radiations of non-catastrophic dimensions should therefore lead to stress-derived radiation hormesis. Other stresses can, in principle, be incorporated into this model. Accordingly, evolutionary and ecological considerations suggest two components of hormesis in relation to ionizing radiation: background radiation hormesis based upon the background exposure to which all organisms on earth are subjected; and stress-derived radiation hormesis. Exposure under stress-derived radiation hormesis is considerably larger than under background radiation hormesis, so significant deleterious effects from non-catastrophic radiation normally may be impossible to detect. Suggestions are provided for testing such postulated deviations from the commonly assumed linear no-threshold (LNT) hypothesis for the biological consequences of exposure to radiation.

Adaptation, Physiological↗

PubMed1998

Buffering: a possible passive-homeostasis role for redundant DNA.

A new general role for redundant (apparently non-coding) DNA is speculated: buffering the effect of fluctuations in intra-cellular solute composition on chromatin condensation state in its condensed form and on binding of DNA-tropic proteins and other ligands in its decondensed form. The "buffering" DNA performing such passive-homeostasis (energy-independent) function, can provide selective advantage in ecological niches with a low energy supply.

Animals↗

PubMed1992

Selegiline--an overview of its role in the treatment of Parkinson's disease.

Selegiline (10 mg per day) selectively inhibits monoamine oxidase type B and thus thwarts the metabolism of dopamine by this enzyme. Selegiline has been used in the therapy of Parkinson's disease since 1986. It enhances the efficacy of levodopa, allows a reduction of the levodopa dose, and improves fluctuations in disability. It also interacts with mechanisms suspected of playing a role in the progression of the disease. Animal studies have shown that selegiline prevents the development of a Parkinson-like syndrome induced by the neurotoxin MPTP. It decreases oxidative stress resulting from the metabolism of dopamine via MAO-B. Clinical studies have shown that selegiline is effective in the therapy of untreated de novo patients: the progression of symptoms demanding the introduction of levodopa into the therapy was delayed, and the risk of needing levodopa treatment within one year was reduced by 57% with selegiline. The mode of action of this drug in the treatment of early Parkinson's disease is still under discussion. There is strong evidence that selegiline may slow the progression of the disease, but a direct symptomatic effect cannot be excluded.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1977

Clinical evaluation of somatostatin as a potential ajunct to insulin in the management of diabetes mellitus.

To determine whether somatostatin, an inhibitor of glucagon and growth hormone secretion, might be useful as an adjunct to insulin the management of diabetic hyperglycaemia, seven insulin-requiring diabetic men were given somatostatin (100 microgram/h, IV) continuously for 3 days after their diabetes had been treated intensively by diet and insulin on a metabolic ward. During infusion of somatostatin and despite reduction in average insulin dose exceeding 50%, there was improvement in diabetic control as assessed by postprandial hyperglycaemia, 24-h glycosuria and the average daily serum glucose level and its fluctuation; when somatostatin was discontinued, but insulin doses held constant, diabetic control rapidly worsened. No adverse effects were observed. These results indicate that somatostatin plus insulin can be a more effective regimen than insulin alone in controlling diabetic hyperglycaemia. A longer acting and more selective somatostatin preparation may prove useful as an adjunct to insulin in the management of diabetes.

Adult↗

PubMed2006

Solution structure and dynamics of the N-terminal cytosolic domain of rhomboid intramembrane protease from Pseudomonas aeruginosa: insights into a functional role in intramembrane proteolysis.

Rhomboids are ubiquitous integral membrane proteases that release cellular signals from membrane-bound substrates through a general signal transduction mechanism known as regulated intramembrane proteolysis (RIP). We present the NMR structure of the cytosolic N-terminal domain (NRho) of P. aeruginosa Rhomboid. NRho consists of a novel alpha/beta fold and represents the first detailed structural insight into this class of intramembrane proteases. We find evidence that NRho is capable of strong and specific association with detergent micelles that mimic the membrane/water interface. Relaxation measurements on NRho reveal structural fluctuations on the microseconds-milliseconds timescale in regions including and contiguous to those implicated in membrane interaction. This structural plasticity may facilitate the ability of NRho to recognize and associate with membranes. We suggest that NRho plays a role in scissile peptide bond selectivity by optimally positioning the Rhomboid active site relative to the membrane plane.

Binding Sites↗